Khoi Chong-Sun, Lin Tzu-Yu, Chiang Chih-Kang
Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City 220216, Taiwan.
Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Taoyuan City 320315, Taiwan.
Antioxidants (Basel). 2024 Dec 5;13(12):1486. doi: 10.3390/antiox13121486.
Excessive intake of free fatty acids (FFAs), especially saturated fatty acids, can lead to atherosclerosis and increase the incidence of cardiovascular diseases. FFAs also contribute to obesity, hyperlipidemia, and nonalcoholic fatty liver disease. Palmitic acid (PA) is human plasma's most abundant saturated fatty acid. It is often used to study the toxicity caused by free fatty acids in different organs, including vascular lipotoxicity. Fatty acid overload induces endothelial dysfunction through various molecular mechanisms. Endothelial dysfunction alters vascular homeostasis by reducing vasodilation and increasing proinflammatory and prothrombotic states. It is also linked to atherosclerosis, which leads to coronary artery disease, peripheral artery disease, and stroke. In this review, we summarize the latest studies, revealing the molecular mechanism of free fatty acid-induced vascular dysfunction, targeting insulin resistance, reactive oxygen species, inflammation, programmed cell death, ER stress, and mitochondrial dysfunction. Meanwhile, this review provides new strategies and perspectives for preventing and reducing the impact of cardiovascular diseases on human health through the relevant targeting molecular mechanism.
过量摄入游离脂肪酸（FFA），尤其是饱和脂肪酸，可导致动脉粥样硬化并增加心血管疾病的发病率。游离脂肪酸还会导致肥胖、高脂血症和非酒精性脂肪肝病。棕榈酸（PA）是人体血浆中最丰富的饱和脂肪酸。它常用于研究游离脂肪酸在不同器官中引起的毒性，包括血管脂毒性。脂肪酸过载通过各种分子机制诱导内皮功能障碍。内皮功能障碍通过减少血管舒张和增加促炎和促血栓形成状态来改变血管稳态。它还与动脉粥样硬化有关，动脉粥样硬化会导致冠状动脉疾病、外周动脉疾病和中风。在本综述中，我们总结了最新研究，揭示了游离脂肪酸诱导血管功能障碍的分子机制，其靶点包括胰岛素抵抗、活性氧、炎症、程序性细胞死亡、内质网应激和线粒体功能障碍。同时，本综述通过相关的靶向分子机制，为预防和减少心血管疾病对人类健康的影响提供了新的策略和观点。
